Molecular diffusion in the human nail measured by stimulated Raman scattering microscopy

Journal ArticleResearch Support, Non-U.S. Gov'tauthors' post-print versionThe effective treatment of diseases of the nail remains an important unmet medical need, primarily because of poor drug delivery. To address this challenge, the diffusion, in real time, of topically applied chemicals into the human nail has been visualized and characterized using stimulated Raman scattering (SRS) microscopy. Deuterated water (D2O), propylene glycol (PG-d8), and dimethyl sulphoxide (DMSO-d6) were separately applied to the dorsal surface of human nail samples. SRS microscopy was used to image D2O, PG-d8/DMSO-d6, and the nail through the O-D, -CD2, and -CH2 bond stretching Raman signals, respectively. Signal intensities obtained were measured as functions of time and of depth into the nail. It was observed that the diffusion of D2O was more than an order of magnitude faster than that of PG-d8 and DMSO-d6. Normalization of the Raman signals, to correct in part for scattering and absorption, permitted semiquantitative analysis of the permeation profiles and strongly suggested that solvent diffusion diverged from classical behavior and that derived diffusivities may be concentration dependent. It appeared that the uptake of solvent progressively undermined the integrity of the nail. This previously unreported application of SRS has permitted, therefore, direct visualization and semiquantitation of solvent penetration into the human nail. The kinetics of uptake of the three chemicals studied demonstrated that each altered its own diffusion in the nail in an apparently concentration-dependent fashion. The scale of the unexpected behavior observed may prove beneficial in the design and optimization of drug formulations to treat recalcitrant nail disease

Drug delivery into microneedle-porated nails from nanoparticle reservoirs

Copyright © 2015. Published by Elsevier B.V.Author's post-print version. The definitive version is available from the publisher via doi: 10.1016/j.jconrel.2015.10.026This study demonstrates the potential of polymeric nanoparticles as drug reservoirs for sustained topical drug delivery into microneedle-treated human nail. Laser scanning confocal microscopy was used to image the delivery of a fluorescent model compound from nanoparticles into the nail. A label-free imaging technique, stimulated Raman scattering microscopy, was applied, in conjunction with two-photon fluorescence imaging, to probe the disposition of nanoparticles and an associated lipophilic 'active' in a microneedle-porated nail. The results provide clear evidence that the nanoparticles function as immobile reservoirs, sequestered on the nail surface and in the microneedle-generated pores, from which the active payload can be released and diffuse laterally into the nail over an extended period of time

Electrochemical Investigations of Hydrogenases : Small Molecule Inhibition and Novel Technological Applications

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Rapid and reversible reactions of [NiFe]-hydrogenases with sulfide

Rapid and reversible binding of sulfide to [NiFe]-hydrogenases (particularly the enzyme from Desulfovibrio vulgaris) under weakly acidic conditions (pH 6) has been studied by protein film voltammetry, which tracks the formation of different species as a function of potential. Sulfide (most likely entering as H2S) rapidly attacks the active site during H2 oxidation. The inactive adduct is formed (and is stable) only at potentials substantially more positive than the comparable species formed with oxygen species and is easily reactivated upon reduction. The sulfide adduct also reacts further with O2 to produce a new species that undergoes reductive activation very slowly. The results clarify complex and controversial chemistry reported in the literature and provide insight into how these enzymes would cope with sulfide production in sulfate-reducing bacteria

Next Generation Digital Pathology: Emerging Trends and Measurement Challenges for Molecular Pathology

Digital pathology is revolutionising the analysis of histological features and is becoming more and more widespread in both the clinic and research. Molecular pathology extends the tissue morphology information provided by conventional histopathology by providing spatially resolved molecular information to complement the structural information provided by histopathology. The multidimensional nature of the molecular data poses significant challenge for data processing, mining, and analysis. One of the key challenges faced by new and existing pathology practitioners is how to choose the most suitable molecular pathology technique for a given diagnosis. By providing a comparison of different methods, this narrative review aims to introduce the field of molecular pathology, providing a high-level overview of many different methods. Since each pixel of an image contains a wealth of molecular information, data processing in molecular pathology is more complex. The key data processing steps and variables, and their effect on the data, are also discussed